Vocal fold scarring is the single greatest cause of poor voice after vocal fold surgery (Hirano, 1995; Woo, Casper, Colton and Brewer, 1994). Such scarring results in replacement of healthy tissue by fibrous tissue, which can irrevocably alter vocal fold function, leading to a decreased or absent vocal fold mucosal wave (Benninger, Alessi, Archer et al., 1996). Even small foci of scar can impede vocal fold function when separation of the body (muscle) and cover (epithelium and the superficial layer of the lamina propria) is compromised. Because there is currently no consistently effective treatment for the scarred vocal fold, it is 1 of the most challenging laryngeal disorders to treat (Thibeault and Ford, 2003) and is the focus of this competing renewal on characterizing taryngeal scars. The long-range aim of this project no longer focuses exclusively on sulcus vocalis, but now encompasses the characterization and treatment of the more universal phenomenon of vocal fold scarring. This long-range objective will be accomplished by characterizing laryngeal scarring and its influence on phonation, both pre-and post-treatment, using 1) controlled laboratory experiments, and 2) computer modeling experiments. The laboratory experiments will investigate treatment effects at the cellular level in animal's tissues and excised larynx models. Building on experiments completed over the last 5 years, we will investigate the role of growth factors and vitamin A in preventing and treating scars, and we will attempt to better characterize scars in the vocal fold and their vibratory consequences. We have found it necessary to combine modeling and systematic laboratory investigations to resolve the complex interactions between tissue characteristics, geometry and surgical requisites necessary to create a suitable clinical outcome. This proposal is timely because no consistently effective treatment modality is known for scarring, and it remains 1 of the unsolved problems of phonosurgery. While our initial 5 years of study have yielded several key hypotheses to guide treatment options, the current proposal will enable us to substantiate and/or further clarify these hypotheses so that they will have a greater impact. [unreadable] [unreadable] [unreadable]